Mammography is a specialized form of radiography designed to detect the subtle changes in x-ray attenuation that are caused by cancerous tissue when x-rays irradiate the human breast. While there is presently no means for preventing breast cancer, early detection of the disease prolongs life expectancy and decreases the likelihood of the need for a total mastectomy. Radiographic mammography is currently the most common method of detecting and analyzing breast lesions. The American Medical Association, The American Cancer Society, and the American College of Radiology recommend yearly mammograms for women beginning at age 40.
Particular features in mammograms that are indicative of breast cancer include spiculated, or stellar-shaped, lesions and microcalcifications. While both features have a relatively high probability of being malignant, both features are also difficult to detect. To detect any feature at all, the x-ray attenuation of that feature must differ appreciably from that of its environment. In the case of cancerous tissue, there is very little difference in attenuation between cancerous tissue and the glandular tissue in which it is found at x-ray energies above about 35 keV and a difference of only about 10% at x-ray energies of about 20 keV. Detection of spiculated masses is further complicated by the presence in typical mammograms of myriad lines corresponding to fibrous breast tissue. In the case of microcalcifications, while they are almost radiopaque, they are usually very small and faint in a mammogram and it is very difficult to distinguish cancerous microcalcifications from numerous other artifacts that are of similar size and appearance.
A typical analog or film-based mammography system 100 is shown in FIG. 1. The system comprises an x-ray tube 110, upper and lower compression paddles 130,135 an anti-scatter grid 140, a screen-film unit 150, and a phototimer detector 160, all of which are mounted on a frame 170. The x-ray tube comprises a cathode 112, an anode 114 that is mounted on a shaft 116 and rotated by a motor 118, a tube port 120, a filter 122 and a collimator 124. The screen-film unit includes an x-ray film 152 and a fluorescent screen 154. Phototimer detector 160 measures the total exposure. A control system (not shown) controls the operation of the x-ray tube including the peak voltage and tube current and terminates operation when a desired exposure as measured by detector 160 has been reached. Advantageously, the control system also includes a subsystem for measuring the space between compression paddles 130, 135 and therefore the thickness of the breast.
To make a mammogram, a patient's breast is compressed between a lower surface 132 of the upper compression paddle 130 and an upper surface 137 of the lower compression paddle; and the x-ray tube is turned on. Motor 118 rotates anode 114 while high energy electrons bombard the rotating anode causing the anode to emit x-rays. Some of the x-rays are emitted through tube port 120 in the direction of the breast located between the two compression paddles. The x-rays are band pass filtered by filter 122 to eliminate x-rays of especially high or low energies and are collimated by collimator 124 to eliminate those x-rays traveling in unwanted directions. The remaining x-rays pass through the breast where they are selectively attenuated and are incident on the anti-scatter grid 140. The x-rays that pass through the anti-scatter grid then pass through the x-ray film with little interaction with the film and are incident on the fluorescent screen 154. The x-rays interact with the fluorescent material in the screen, causing this material to emit radiation that interacts with the x-ray film to produce the x-ray image. Some of the x-rays also pass through the fluorescent screen and are incident on the phototimer detector 160.
A variety of choices are available in the physical properties of these systems. The optimal x-ray energy range for these systems is about 17 to 23 keV. Within this range, molybdenum has characteristic x-ray peaks at 17.5 and 19.6 keV and rhodium has such peaks at 20.2 and 22.7 keV; and anodes made of one or the other of these elements are widely used. Typically, the tube port is made of beryllium which has low attenuation. The filters are typically made of the same material as the anode but a rhodium filter is also used with a molybdenum anode for imaging thicker and denser breasts.
Ideally, the mammography system forms on film 152 a projection image of the attenuation of x-ray photons that traveled on straight lines from the anode through the breast to the film. However, the distribution of photons incident per unit area on the film is not uniform. Absorption of photons within the anode creates a “heel effect” as a result of which the area of the film directly under the anode will receive significantly fewer photons per unit area than the area of the film under the cathode.
The photons may also be redirected by Compton or Rayleigh scattering and arrive at the film from many different angles other than angles corresponding to a straight line from the anode. Such scattered photons reduce the contrast in the mammogram. The amount of scatter in mammography varies with increasing breast thickness and breast area. For a typical 5 cm-thick breast, the contrast reduction due to scatter is on the order of 33%. To reject scatter, parallel linear grids with a grid ratio of 4:1 to 5:1 are commonly used. While the film is exposed, the grids are oscillated over a short distance to blur the grid lines. A cellular grid structure is also used in some systems to reject scatter in two dimensions.
Various screen film systems are available from suppliers such as Agfa, Fuji and Kodak. All of these systems have a single gadolinium oxysulfide phosphor screen which produces green light and a green-sensitive single emulsion film. A variety of different speed films are available; and the characteristic curves of optical density versus exposure of these films can be quite different. Typical characteristic curves for two screen-film systems are shown in FIG. 2. Of particular note, the contrast in an image is a function of the slope of the characteristic curve.
Recently, mammography systems have become available that use digital detectors in place of a screen-film system. These systems produce digital mammograms without the intervening steps of processing a film and then digitizing it. The digital systems introduce considerably more variability in the process conditions. In addition to replacing the screen film combination, they also use different anode targets (typically, tungsten) and possibly other filters.
In addition to variations in the physical properties of the mammography system, numerous operational parameters are within the control of the operator. These include the x-ray energy, typically specified in peak voltage (kVp), the exposure, typically specified in milli-Ampere-seconds (mAs), and the processing of the x-ray film. Another factor that clearly affects the optical density recorded on the film is the thickness of the breast being x-rayed and its density (or proportion of glandular tissue to total breast thickness). To a limited degree, the thickness of the breast being x-rayed can be controlled by the operator by adjusting the pressure exerted by the upper compression paddle.
Despite the large number of physical and operational variables that exist in mammography systems, these differences are not an issue when reading a single set of mammograms taken at the same time under the same conditions. In reading the mammograms, the radiologist's attention is focused on the relative difference between adjacent regions of the mammogram; and since the mammogram was made under one set of conditions; these conditions have little effect on relative differences. However, the radiologist frequently wants to compare one set of mammograms with another set of mammograms, for example, a set of mammograms taken the previous year for the same person. In this case, there may be substantial differences between the two sets, for example, because they were taken on different systems, or recorded on different films, or taken with x-rays of different energy, or for different exposures. Needless to say, there are also substantial differences between film-based mammograms and digital mammograms. Similar issues arise in analyzing mammograms of different persons.
Efforts have been made to address these problems by abstracting out at least some of the differences attributable to the physical and operational variables. In Mammographic Image Analysis (Kluver 1999), Ralph Highnam and Michael Brady describe how to correct and remove the effects of x-ray scatter, x-ray energy (kVp), exposure (mAs) and breast thickness. See also, their PCT application PCT/GB00/00617 filed Feb. 21, 2000 and published as publication WO 00/52641 on Sep. 8, 2000, which is incorporated herein by reference. The result is a completely physical description of the breast in terms of thickness and type of material—fat or glandular tissue. Their interest is in the glandular or interesting tissue and they call this description Hint, which is expressed in units of centimeters. A complete physical description of the breast would require a combination of Hint and either the total breast thickness, Htot, or the fat thickness, Hfat, where Htot=Hint+Hfat.
However, the Hint image is very difficult for the radiologist to interpret since it is radically different from the conventional image the radiologist has been trained to interpret. Moreover, the computations needed to produce the Hint image are extensive and require substantial amounts of processing time.
Another approach is described in U.S. Pat. No. 6,516,045 for “Device and Method for Determining Proportions of Body Materials”, which is incorporated herein by reference. As shown in FIG. 3, in this technique, two right-angled wedge-shaped reference materials 302, 304 are positioned alongside the breast 306 between the compression paddles. One wedge has the attenuation characteristics of fat. The other wedge has the attenuation characteristics of glandular tissue. The base of each wedge is the thickness of the breast. As a result, when the mammogram is formed, an image is created of the wedges as well as the breast and the optical density of the image of the wedges ranges continuously from a value corresponding to 100% fat to 100% glandular tissue. Since the shape of the wedges is known, the optical density of each point in the image of the wedges can be associated with a specific percentage of fat and glandular tissue. Then by matching each pixel of the breast image with the pixels of the wedge having the same optical density, the percentage of fat and glandular tissue at that pixel in the breast image can be determined.
Still another approach is described in the co-pending applications Ser. No. 09/992,059 for “A Method and Apparatus for an Improved Computer Aided Diagnosis System,” and Ser. No. 10/079,327 for “A Method and Apparatus for Expanding the Use of Existing Computer-Aided Detection Code” of which the present application is a continuation-in-part. In those applications, various normalization techniques are described to remove the differences caused by different detectors. In particular, the applications describe a variety of techniques for equalizing the contrast response in which analytic expressions or “look-up” tables are developed that convert the response measured by one system to what the response would be if measured by another system. While these techniques facilitate the analysis and comparison of mammograms made using different detectors, they do not address differences arising from different exposure parameters or differences in breast thickness.
Another area in which it would be advantageous to compensate for differences arising from different exposure parameters or differences in breast thickness is in the development of algorithms for computer aided detection and diagnosis of abnormalities in medical images such as mammograms.
The algorithms that are presently used are heavily dependent on the training of the algorithms using groups of mammograms. See, for example, U.S. Pat. No. 5,491,627 to Zhang et al., U.S. Pat. No. 6,075,879 to Roehrig et al., and the above-referenced Ser. No. 10/079,327 for “A Method and Apparatus for Expanding the Use of Existing Computer-Aided Detection Code.” At present, to obtain a sufficient number of mammograms for training purposes, the set of training mammograms includes mammograms formed on different mammographic systems. As a result, the performance of the computer aided detection system is not as great as it would be if the training had been performed on the same sized set of mammograms made on a single system. It would be advantageous to be able to train the detection algorithm using larger sets of mammograms made on effectively the same mammographic system.